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Horizontal Gene Transfer Common Among Human-Associated Bacteria

NEW YORK (GenomeWeb) – Bacteria associated with the human body exchange genes more often than bacteria that are not linked to humans, according to a new analysis.

Horizontal gene transfer is a common method through which prokaryotes exchange genes, including antibiotic resistance genes and virulence factors. An international team of researchers has now adapted a phylogeny-based detection method to examine the occurrence of horizontal gene transfer among human-associated bacteria.

By analyzing data from the Human Microbiome Project, the researchers found that more than half the genes of the human microbiome had at one point gone through a transfer, as they reported this week in Scientific Reports. While some of these transfers involved bacteria living in similar niches, many involved bacteria living in different parts of the body, raising questions of how the gene transmission occurred.

"A better understanding of this phenomenon also will have significant public health value, since the emergence of multidrug resistant pathogens as a result of the horizontal spread of antibiotic resistant genes has become a global concern," senior author Arshan Nasi from COMSATS University Islamabad in Pakistan said in a statement.

He and his colleagues modified the HGTree pipeline, which relies on a combination of parsimony, neighbor joining, and maximum likelihood approaches, to construct gene trees, which they then compared to 16S rRNA species reference trees. From this, they could identify candidate horizontal gene transfer events.

In particular, they applied this tool to data from the NIH Human Microbiome Project that spanned more than 1,000 bacterial genomes collected from six body sites: the gut, skin, mouth, blood, urogenital tract, and airway.

After establishing that there was unlikely to be large-scale contamination in the dataset, the researchers constructed more than 80,000 gene trees that they then compared to corresponding 16S rRNA gene alignment to uncover about 55,000 genes affected by horizontal gene transfer in the HMP dataset.

When the researchers compared the number of horizontal gene transfers within the Human Microbiome Project genomes to environmental microorganisms, they found that the rate of such transfers was about 30 percent higher among human-associated bacteria.

"This implies that our bodies provide a niche that is unique and facilitates innovation at the microbe level," co-author Gustavo Caetano­-Anollés from the University of Illinois said in a statement.

Some of these gene transfers were local events, while others appeared to be more long-range occurrences. Of the more than 511,000 horizontal gene transfer events the researchers uncovered in the Human Microbiome Project dataset, 40 percent were intra-niche transfers, while 60 percent were inter-niche transfers.

Intra-niche horizontal gene transfers, the researchers said, were likely the result of proximity and shared ecology. The researchers also reported that gene transfer events were more common between closely related bacterial species.

But how inter-niche horizontal gene transfers — such as between bacteria in the gut and bacteria in the urogenital tract — occurred raises more questions. The researchers offered two possible explanations for the high number of inter-niche transfers they observed: that the transfer pre-dates human colonization and thus did not occur within the human body or that bacterial DNA or bacteria themselves could be transferred through the bloodstream, despite that typically being associated with a disease state.

Nasir added in a statement that further research was needed to examine the mechanism of inter-niche horizontal gene transfers.

The researchers added that this phylogeny-based horizontal gene transfer detection approach could further be applied to other metagenomic datasets and to examine the interactions between humans and microbes.